The present invention relates to a process for producing trifluoromethyl-substituted 2-alkoxyacetophenone derivatives, which are important intermediates for medicines and agricultural chemicals, and to intermediates obtained in the process.
Of trifluoromethyl-substituted 2-alkoxyacetophenone derivatives, only 3′-trifluoromethyl-2-methoxyacetophenone and 4′-trifluoromethyl-2-methoxyacetophenone are known. These compounds can be produced by the following processes. Synthesis (1999), (9), 1558–1560 discloses a process of reacting an ylide (generated from methoxymethyltriphenylphosphonium chloride and phenyl lithium) with 4-trifluoromethylbenzonitrile. Tetrahedron (1979), 35(15), 1807–1815 discloses a process of reacting methoxyacetonitrile with 3-trifluoromethylphenylmagnesium bromide or 4-trifluoromethylphenylmagnesium bromide. J. Am. Chem. Soc. (1970), 92, 311–320 discloses a process of reacting 4′-trifluoromethyl-2-diazoacetophenone with methanol. These processes may not be suitable as industrial production processes for producing trifluoromethyl-substituted 2-alkoxyacetophenone derivatives, due to the use of an expensive reagent excessively and the use of an explosive reagent (see J. Organometallic Chem., 390(1990), 275–292).
Tetrahedron (1994), 50(35), 10539–10548 discloses a reaction of 4-methoxy phenacyl bromide or 4-bromo phenacyl bromide with sodium methoxide.
Japanese Patent Application Publication 2001-72638 discloses a process for producing α-bromoalkylphenones by reacting alkylphenones with bromine in a lower alcohol and then by treating the obtained reaction liquid with an acid. It is disclosed in this publication that specific examples of the lower alcohols are methanol, ethanol and propanol.